The objective of our proposed research is to develop a safe, efficient and economical method for administering enzyme therapy for the treatment of various types of cancers and other disorders such as hereditary enzyme defects. We have prepared active, stable complexes of E. coli L-asparaginase immobilized on collagen membranes and demonstrated $ the ability of these complexes to reduce serum asparagine levels in healthy dogs efficiently and safely when administered by extracorporeal perfusion. The specific goals of this proposal are: (1) to prepare active, stable complexes of collagen with glutaminase and with phenylalanine ammonia lyase and to evaluate the ability of these membranes to reduce the concentrations of their respective substrates in the serum of healthy dogs and (2) to bind asparaginase, glutaminase and phenylalanine ammonia lyase to bovine collagen arterial heterografts and reconstituted bovine collagen tubes and to implant these as immobilized enzyme vascular prostheses. These enzymes have demonstrated antineoplastic activity, but parenteral therapy is severely limited by low circulating times, toxicity and antigenicity. The proposed system bypasses these limitations and may provide two entirely new approaches for effective enzyme therapy of cancers and other disease -extracorporeal therapy for intermittent short-term treatment and an implant for continuous long-term treatment.